ProjectSummary/Abstract Chromatinorganizationandepigenomicmodificationssuchascytosinemethylationplayinstrumentalroles ingeneregulationduringhumandevelopmentandinhealthyanddiseasestates.Althoughthegenomeis nearlyidenticalineachcellinthehumanbody,chromatinconformationandcytosineDNAmethylationare highlydynamicacrosscelltypesandduringdevelopment.Previousstudiesshowedthatchromatinlooping canberegulatedbycytosinemethylation.However,ourcurrentstateofknowledgeoftheinteractions betweenchromatinorganizationandDNAmethylationisbuiltonanalyzingculturedcellsandbulktissues. Theinteractionbetweencell-typespecificchromatinloopingandmethylationinheterogeneoustissues remainlargelyunexplored.Thisprojectwilldevelopsingle-cellmulti-omicmethodstojointlyanalyze chromatinconformationandcytosinemethylationfromthesamecell.Themethodswillleadtohighquality cell-typespecificchromatinconformationmapsofhumantissue,andtheanalysisoftherelationship betweenchromatinconformationandcytosinemethylation.Ifsuccessful,theproposedmethodswillgreatly facilitatethestudyofgeneregulationincomplexhumantissuesandinheterogeneousdiseasessuchas cancer.